Study On The Interaction Between Genetic Polymorphisms And Ernvironmental Risk Factors To Esophageal Cancer In Huai-An Population

Objective: The highest incidence rate of malignant tumor is esophageal cancer in Huai-an. It is the results of the interaction between environmental and genetic factors. The current study analyzed the interaction between genetic polymorphisms and environmental risk factors to esophageal cancer in Huai-an population.Methods: A hospital-based 1:1 case-control study was conducted among 106 esophageal cancer patients and 106 controls who had no disease history of cancer and digestive system. These patients were diagnosed as primary esophageal cancer. The questionnaire included items on smoking status, alcohol consumption, diet and drinking habit, et al. Each of cases and controls provided 5ml peripheral blood sample to extract DNA. PCR-RLFP technique was used for analyzing genotypes of CYP1A1, CYP2E1, GSTM1, GSTT1, XRCC1 and XPD. The risk factors were screened by multivariate conditional logistic regression model and the PAR was calculated. The interaction between genes and environmental risk factors was analyzed by multivariate logistic regression model.Results: The results showed that the polymorphisms of XRCC1 Arg399Gln were related to the susceptibility of esophageal cancer. The Gln/Gln genotype frequency was significantly higher in the cases than controls. The interaction between polymorphisms of metabolic enzyme genes and repair genes was analyzed. It was revealed the combined genotypes of both CYP2E1 (wt/mt+mt/mt) and GSTT1 (null) had an antagonistic joint action in risk of esophageal cancer. Similarly, there was an antagonistic joint action between XRCC1 399codon (Arg/Gln+Gln/Gln) and 194condon (Arg/Trp+Trp/Trp). The environmental risk factors related with esophageal cancer were deep of smoking, hobby of hot or cold food, frequent consumption of pickled food, kinds of drinking and family history of digestive tumor. The population attributable risk of the five factors was 23.56%, 18.07%, 29.58%, 29.29% and 25.13%, respectively. Summary population attributable risk for the five factors was 72.79%. Combination analysis of environmental risk factors and polymorphisms of genes showed that there was a synergistic effect on development of esophageal cancer between CYP1A1 mutation genotype and smoking; between XRCC1 399codon (Arg/Gln+Gln/Gln) and hobby of hot or cold food; between GSTT1 (null) and drinking well-water; between CYP2E1 and family history of digestive tumor. These synergistic effects increased the risk of esophageal cancer. Conclusion: The results of this study show that although genetic factors have an effect on the incidence of esophageal cancer, the main risk factors are environmental factors. The attention should focus on the interaction between genetic polymorphisms and environmental risk factors. These results provide foundation of theory on the etiology, decreasing morbidity and mortality of esophageal cancer, and making primary preventive project.